Highly fluorinated organic compounds, and particularly perfluorocarbon compounds, are well known to be both stable and chemically inert. During the past 25 years much attention has focused on the use of such compounds in biological systems because they are capable of dissolving and transporting large amounts of oxygen. These properties make them potentially useful as contrast media, oxygen transport agents or "artificial bloods" in the treatment of heart attack, stroke, and other vascular obstructions, as adjuvants to coronary angioplasty, and in cancer radiation treatment and chemotherapy.
Among the highly fluorinated organic compounds that are said to be useful in such applications are perfluorocarbon compounds, e.g., perfluorodecalin, perfluoroindane, perfluorotrimethyl bicyclo [3.3.1] nonane, perfluoromethyl adamantane, perfluorodimethyl adamantane, and perfluoro-2,2,4,4-tetramethylpentane; 9-12C perfluoro amines, e.g., perfluorotripropyl amine, perfluorotributyl amine, perfluoro-1-azatricyclic amines; bromofluorocarbon compounds, e.g., perfluorooctyl bromide and perfluorooctyl dibromide; F-4-methyl octahydroquinolidizine and perfluoro ethers, including chlorinated polyfluorocyclic ethers. Such compounds are described, for example, in U.S. Pat. Nos. 3,962,439, 3,493,581, 4,110,474, 4,186,253, 4,187,252, 4,252,827, 4,423,077, 4,443,480, 4,534,978, 4,686,024, 4,865,836, 4,866,096 and 4,868,318, European patent applications 80710 and 158,996, British patent specification 1,549,038 and German Offen. 2,650,586.
For intravenous use, highly fluorinated organic compounds must be dispersed as emulsions. See, e.g., L. C. Clark: Jr. et al., "Emulsions Of Perfluorinated Solvents For Intravascular Gas Transport," Fed. Proc. 34(6), pp. 1468-77 (1975); K. Yokoyama et al., "A Perfluorochemical Emulsion As An Oxygen Carrier," Artif, Organs (Cleve), 8(1), pp 34-40 (1984); and U.S. Pat. Nos. 4,110,474 and 4,187,252. Neat, highly fluorinated organic compounds are immiscible in blood.
U.S. Pat. No. 3,991,138 discloses perfluorocarbon emulsions as artificial bloods having fluorocarbons that may be excreted from the animal body within a clinically acceptable time period. In the '138 patent, for example, perfluorocyclocarbons were found to leave the animal body at a faster rate than other perfluorocarbons. In contrast, when perfluorocarbon ethers were administered to an animal, they were found to reside in the liver and spleen rather indefinitely. More recently, a hydrofluoroalkyl ether, F[CF(CF.sub.3)CF.sub.2 O].sub.4 CFHCF.sub.3, has been tested as a synthetic blood emulsion, but it also tends to stay in the body, see Chem. Pharm. Bull., 33, 1221 (1985). In general, the perfluorocarbon ethers have been regarded as unsatisfactory candidates for use as oxygen transport agents and for medical purposes because they tend to reside rather indefinitely in the animal body.
In view of the above background, the search continues for emulsions containing perfluorocarbons that function effectively as oxygen transport agents and that may be excreted from the body within a clinically acceptable time period. Such emulsions must not only contain a high enough concentration of the highly fluorinated organic compound to be effective at the desired level of oxygen transport, they must also be capable of sterilization, preferably by heat, have long term stability in the fluid or non-frozen state, persist for sufficiently long times in the blood stream to deliver useful quantities of oxygen and yet be eliminated rapidly enough from the body to avoid toxicity and retention in body parts and organs.